title: Protonation-dependent conformational variability of intrinsically disordered proteins.
abstract: Intrinsically disordered proteins (IDPs) are characterized by substantial conformational plasticity and undergo rearrangements of the time-averaged conformational ensemble on changes of environmental conditions (e.g., in ionic strength, pH, molecular crowding). In contrast to stably folded proteins, IDPs often form compact conformations at acidic pH. The biological relevance of this process was, for example, demonstrated by nuclear magnetic resonance studies of the aggregation prone (low pH) state of α-synuclein. In this study, we report a large-scale analysis of the pH dependence of disordered proteins using the recently developed meta-structure approach. The meta-structure analysis of a large set of IDPs revealed a significant tendency of IDPs to form α-helical secondary structure elements and to preferentially fold into more compact structures under acidic conditions. The predictive validity of this novel approach was demonstrated with applications to the tumor-suppressor BASP1 and the transcription factor Tcf4.
authors.affiliation: Department of Computational and Structural Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, A-1030, Vienna, Austria.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Geist
authors.forename: Morkos A
authors.initials: MA
authors.lastname: Henen
authors.forename: Sandra
authors.initials: S
authors.lastname: Haiderer
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Schwarz
authors.forename: Dennis
authors.initials: D
authors.lastname: Kurzbach
authors.forename: Anna
authors.initials: A
authors.lastname: Zawadzka-Kazimierczuk
authors.forename: Saurabh
authors.initials: S
authors.lastname: Saxena
authors.forename: Szymon
authors.initials: S
authors.lastname: Zerko
authors.forename: Wiktor
authors.initials: W
authors.lastname: Koźmiński
authors.forename: Dariush
authors.initials: D
authors.lastname: Hinderberger
authors.forename: Robert
authors.initials: R
authors.lastname: Konrat
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009994:Osmolar Concentration; D011487:Protein Conformation; D011522:Protons; D012097:Repressor Proteins / Q000737:chemistry*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: C104089:BASP1 protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D064267:Intrinsically Disordered Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D012097:Repressor Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors
keywords: EPR spectroscopy; biomolecular NMR; intrinsically disordered proteins; pH dependence; protein meta-structure; structural biology